Assessment System of Drug Absorption by Cultured Cells, and Control of Whole Study. Caco-2 cell monolayr system for absorption was established. The absorptions were well correlated with the results in human colon. The absorption from the bioadhesive microsphere (MS) developed by Meiji Seika group was determined in this system. Polycarbophil (PCP) that is used for adhesive coating exhibited absorption enhancement. MS coated with decanoyl carnitine(absorption enhancer)and PCP showed more 10 times absorbability than control, showing the promise of adhesive MS.Cationic polyamino acids showed the possibility to be used as adhesive coating material with absorption enhancement. Absorbability of Polypeptides and Prodrug in Peyer's Patch. Concanavalin (Con A) , a rectin, that is expected to target to Peyer's patch (PP) was conjugated with BSA in the ratio 1/1 (maleimide method) . This conjugate showed higher permeability in PP than BSA itself. This showed the possibility to use rectin protein c
… Moreonjugate as a prodrug for absorption enhancement. Polylacetic acid Polyglycolic acid copolymer MS was prepared as DDS for PP.The absorption of BSA,HRP and SOD from the MS was examined, but the determination of transported amounts of these compounds in this system remained as future problem. Development of Membrane Adhesive Micorosphere (MC) and MS targeted to PP.The adhesive MC was not prepared because of surface activity of the enhancers encapsulated in MC.since MS can be substituted, the adhesive MS preparation was examined. PVP as base was found unsuitable, because the prepared MS shapes were not uniform. Gelatine MS coated with PCP exhibited enough adhesiveness with good release.分担課題:ポリペプチド及びそのプロドラッグのパイエル板吸収性 ウサギ小腸パイエル板(PP)に指向性があると考えられるレクチンの一種concavalin A(Con A)とBSAとを1:1で架橋したconjugateを純度よく合成することに成功した(マレイミド法)。これのパイエル板透過性は単独のものよりも増大した。これにより蛋白質の透過性を改善するプロドラッグの可能性が示された。パイエル板指向性の剤形としてポリ乳酸-ポリグリコール酸共重合体を用いたMSを調整し、これにBSA,HRP,SODなどを封入して、パイエル板透過性を検討したが、透過量の定量に今後の課題が残された。分担課題:粘膜接着性マイクロカプセル(MC)及びパイエル板指向性のマイクロスフェア-の開発 上記のMCの調製を検討したが、封入する吸収促進剤の界面活性作用のためこれは成功しなかった。MSでも目的にはかなうので、これの調製を検討した。基剤として先ず、PVP検討したが、形状がそろわなかった。ゼラチンを基剤とし、PCPで表面をコーティングすることにより、放出性の良好な目的とするMSの調製に成功した。 Less